The principal objective of this proposal is to further characterize the process of ovarian follicular maturation and ovulation. In most endocrine systems a steady state prevails. An external stimulus produces an oscillation with a more or less rapid return to equilibrium. In the reproductive system, the growth and maturation of the ovarian follicle, the process of ovulation and of subsequent corpus luteum formation are events occurring without a tendency toward equilibrium. Each aspect of the sequence of events appears to proceed towards a climax under conditions which appear to be partially self sustained and self-terminated and therefore, which require novel control mechanisms. It is our ultimate purpose to define these control mechanisms through experiments in humans, in organ culture, and ultimately in cell free systems. We plan to study gonadotropin and ovarian steroid hormone secretion in response to a number of stimuli in normal women and women with disorders of follicular maturation in order to better characterize the operation of the hypothalamic pituitary feedback mechanism. By study of ovarian hormone secretion, follicular fluid steroid concentration and steroid synthesis by thecal, granulosa and interstitial cells isolated from the same ovary, aspects of internal ovarian regulation may be elucidated. Finally culture of isolated granulosa cells and if possible theca interna will be undertaken to evaluate control mechanisms for estrogen secretion. This project is intended both to advance our knowledge of the reproductive cycle and to provide information relevant to the development of new population control procedures.